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      Anti-CD20 therapies and pregnancy in neuroimmunologic disorders : A cohort study from Germany

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          Abstract

          Objective

          To report pregnancy outcomes and disease activity (DA) in women with MS, neuromyelitis optica spectrum disorders (NMOSDs), and other neuroimmunologic diseases (ONID) after treatment with rituximab (RTX)/ocrelizumab (OCR) 12 months before or during pregnancy.

          Methods

          Data were collected in the German MS and pregnancy registry and centers from the Neuromyelitis Optica Study Group. Sixty-eight known outcomes of 88 pregnancies from 81 women (64 MS, 10 NMOSD, and 7 ONID) were included and stratified in 3 exposure groups: >6M-group = RTX/OCR >6 but ≤12 months before the last menstrual period (LMP) (n = 8); <6M group = RTX/OCR <6 months before the LMP (n = 47); preg group = RTX/OCR after the LMP (n = 13).

          Results

          Pregnancy outcomes were similar between groups, but significantly more preterm births (9.8% vs 45%) occurred after exposure during pregnancy. Overall, 2 major congenital abnormalities (3.3%), both in the preg group, were observed. Three women had severe infections during pregnancy. All women with MS (35) and 12/13 women with NMOSD, RTX/OCR exposure before the LMP and known pregnancy outcomes after gestational week 22 were relapse free during pregnancy. Five of 29 (17.2%) women with relapsing-remitting MS (RRMS) and 1 of 12 (8.3%) with NMOSD and at least 6 months postpartum follow-up experienced a relapse postpartum. Duration of RTX/OCR and early retreatment but not detection of B-cells were possible predictors for postpartum relapses in patients with RRMS/NMOSD.

          Conclusions

          Although RTX/OCR might be an interesting option for women with RRMS/NMOSD who plan to become pregnant to control DA, more data on pregnancy outcomes and rare risks are needed.

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          Most cited references36

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          Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

          The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.
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            One method of evaluating the degree of neurologic impairment in MS has been the combination of grades (0 = normal to 5 or 6 = maximal impairment) within 8 Functional Systems (FS) and an overall Disability Status Scale (DSS) that had steps from 0 (normal) to 10 (death due to MS). A new Expanded Disability Status Scale (EDSS) is presented, with each of the former steps (1,2,3 . . . 9) now divided into two (1.0, 1.5, 2.0 . . . 9.5). The lower portion is obligatorily defined by Functional System grades. The FS are Pyramidal, Cerebellar, Brain Stem, Sensory, Bowel & Bladder, Visual, Cerebral, and Other; the Sensory and Bowel & Bladder Systems have been revised. Patterns of FS and relations of FS by type and grade to the DSS are demonstrated.
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                Author and article information

                Contributors
                Journal
                Neurol Neuroimmunol Neuroinflamm
                Neurol Neuroimmunol Neuroinflamm
                nnn
                NEURIMMINFL
                Neurology® Neuroimmunology & Neuroinflammation
                Lippincott Williams & Wilkins (Hagerstown, MD )
                2332-7812
                January 2021
                17 December 2020
                : 8
                : 1
                : e913
                Affiliations
                From the Institute of Clinical Neuroimmunology (T.K., I.M.), Biomedical Center and University Hospital, Ludwig-Maximilians Universitaet München, Munich; Department of Neurology (S.T., A.I.C., I.A., K.H.), Katholisches Klinikum, St. Josef Hospital, Ruhr University Bochum; Institute of Clinical Pharmacy and Pharmacotherapy (A.I.C.), Heinrich Heine University Düsseldorf; Department of Neurology (A.B.), University Hospital of Augsburg; Klinik für Neurologie (F.H.), Krankenhaus Martha-Maria Halle-Dölau gGmbH, Halle (Saale); Klinik für Neurologie (U.H.-v.O.), Knappschaftskrankenhaus Dortmund Klinikum Westfalen, Dortmund; Marianne-Strauß-Klinik (M.-M.H.), Berg; Department of Neurology (J.K.), Klinikum der Stadt Ludwigshafen gGmbH, Ludwigshafen; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich Heine University Düsseldorf; Department of Neurology (M.R.), Center for Neurology and Neuropsychiatry, LVR-Klinikum Düsseldorf; Department of Neurology (M.S.), University of Leipzig; Sektion Neuroimmunologie (A.W.), Klinik für Neurologie, Klinikum Herford; Institute of Neuropathology and Department of Neurology (M.S.W.), University Medical Center, Georg August University Göttingen, Germany.
                Author notes
                Correspondence Dr. Hellwig zirkuszelt@ 123456hotmail.com

                Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.

                [*]

                These authors contributed equally to this work.

                The Article Processing Charge was funded by the authors.

                Article
                NEURIMMINFL2020031732
                10.1212/NXI.0000000000000913
                7757754
                33334856
                bb318ecd-083f-467a-b9f6-af046cf73f3d
                Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                History
                : 02 June 2020
                : 06 October 2020
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